Eicosanoids And Arthritis

Front 1

Aloprostadil
Class?
Clinical Uses?

Back 1

Aloprostadil

Class: PGE1

Clinical Uses:
1. Helps to maintain patency of ductus arteriosus - used clinically to maintain maternal/fetal blood flow
2. Impotence

Front 2

Misoprostrol
Class?
Clinical Uses

Back 2

Misoprostrol

Class: PGE1 analog

Clinical Uses:
1. Helps to promote ulcer healing in gastric mucosa

Front 3

Carboprost Tromethamine
Class?
Clinical Use?

Back 3

Carboprost Tormethamine

Class: Hemabate solution

Clinical Use:
1. Given by injection to help induce labor

Front 4

Dinoprostrone
Class?
Clinical Use?

Back 4

Dinoprostrone

Class: PGE2

Clinical Use:
1. Administered via SUPPOSITORY to help induce labor
- Facilitate labor by promoting ripening and dilation of the cervix

Front 5

Epoprostenol
Class?
Clinical Uses?

Back 5

Epoprostenol

Class: PGI2

Clinical Uses:
1. Dilate Pulmonary Artery

Front 6

General Consideration for NSAIDs
Tolerance?
Etiology of Side Effects?
Affect on underlying disease?
Which Drug?

Back 6

General considerations fo NSAIDs

Tolerance - There is no tolerance development with NSAIDs

Side Effects - Stem from the underlying changes in TXA2 and Prostaglandin levels

Affect on underlying disease - NSAIDs have no effect on underlying disease

Drug?
Usually empirically chosen based on pharamcokinetics and patient response

Front 7

Pharmacology of NSAIDs
Therapeutic Actions?
Side Effects?

Back 7

Pharmacology of NSAIDs

Therapeutic Actions
1. Pain Relief (Analgesia)
2. Reduce fever (Antipyretic)
3. Anti-inflammatory - (Except Acetaminophen)
4. Prophylactic to reduce risk of MI (Aspirin)
5. These drugs provide symptomatic relief but do not affect the underlying disease.

Side Effects
1. Gastric Irritation
2. Altered respiration
3. Disturbances in Acid/Base balance
4. Increased bleeding
5. Prolongation of Gestation
6. Potential Renal Damage

Front 8

Aspirin Toxicity

Back 8

Aspirin Toxicity
1. Epigastric distress, nausea, vomiting; gastric ulceration, hemorrhage, exacerbate ulcers

2. Inhibit platelet aggregation and prolong bleeding

3. Other cardiovascular actions minimal except with toxic concentrations which can depress circulation

4. Aspirin intolerance, hypersensitivity (skin eruptions, asthma, anaphylaxis)

5. Increased risk of developing Reye’s Syndrome (persistent or recurrent vomiting, listlessness, irritability, combativeness, disorientation or confusion, delirium, convulsions, loss of consciousness- prognosis linked to severity of brain swelling)

6. Hepatotoxicity

7. Acute renal insufficiency in patients with underlying disease (i.e. liver disease with ascites, CHF, renal disease)

8. Low doses decrease urate excretion, antagonize actions of uricosurics and worsen gout

Front 9

Aspirin Poisoning
Primary Effects?
Secondary Effects?

Back 9

Aspiring Poisoning

Primary Effects?
1. CNS - Tinnitus, mental confusion, hearing loss, convulsions, coma
2. GI - Nausea, vomiting
3. Hyperthermia (Uncoupling of Oxidative Phosphorylation), dehydration
4. Stimulation of the respiratory center

Secondary Effects
1. Respiratory Alkalosis
2. Metabolic acidosis
3. Water and electrolyte loss
4. Cardio and Respiratory arrest with severe intoxication.

Front 10

Aspirin Contraindications

Back 10

Aspirin Contraindications
1. Ulcer patients
2. Patients allergic to aspirin
3. Patients with clotting disorders
4. Pregnancy
5. Gout (only high doses are uricosuric -- will increase uric acid excretion from the kidney)
6. Viral infections in children and young adults - Reyes Syndrome

Front 11

Acetaminophen Pharmacology
Effects?
Who should get Acetaminophen?
Overdose?

Back 11

Acetaminophen Pharmacology
Effects:
1. Analgesic and anitpyretic
2. Not useful as an anti-inflammatory agent
3. Weak effects on platelets and no effect on bleeding time
4. No uricosuric effects
5. No alterations in acid- base balance
6. Minimal effects on GI tract at therapeutic doses

Advantageous in the following patients:
- Peptic ulcer, asprin intolerance, anticoagulants
- Children and young adults with viral infections
- Clotting Disorders
- gout

Overdose - Potentially fatal Hepatic Necrosis

Front 12

Treatment for Acetaminophen Overdose?

Back 12

N-Acetylcysteine (IV or orally)
- Essentially a glutathione analog.

Front 13

Indomethacin
Class?
Clinical Uses?
Toxicity?

Back 13

Indomethacin

Class: NSAID - Indole and indene Acetic Acids

Uses:
1. Typical NSAID uses
2. Patent Ductus Arteriosus

Toxicity:
HIGH TOXICITY

Front 14

Ibuprofen
Class?
Advantages?

Back 14

Ibuprofen

Class: NSAID - Arylpropionic Acid

Advantage: Less GI side Effects

Front 15

Narproxen
Class?
Advantages

Back 15

Naproxen

Class: NSAID - Arylpropionic Acid

Advantage: Twice daily dosing - don't need to to take as often.

Front 16

Celecoxib
Class?
Clinical Uses?
Toxicity?

Back 16

Celecoxib

Class: Selective COX-2 Inhibitor

Clinical Uses
- Incidence of GI side effects and renal toxicity less then other NSAIDs
- No signigicant inhibition of platelet aggregation

Toxicity:
1. Note: These drugs have been largely removed form the market because of potential for MI or stroke in patients with underlying cardiovascular disease
2. Celecoxib is contraindicated in patients with sulfa sensitivity, reports of GI bleeding and ulceration

Front 17

Immunosuppressants for Inflammatory Disease
Drugs in class?
Mechanism?
Side Effects?

Back 17

Immunsuppressants for Inflammatory Disease

Drugs: Azathiopurine, methotrexate, leflunomide, pencillamine

Mechanism:
1. There drugs attenuate both inflammation and the destructive process (NSAIDs only treat symptoms)
2. Aggressive therapy with drugs is proving useful in RA
3. Combination therapy with biological modifiers improves outcome

Side Effects: Must be stopped within 1-2 years
1. Infections, fever and chills
2. Anorexia, GI distress
3. Hepatotoxicity
4. Agranulocytosis, Anemia
5. Leukopenia/Thrombocytopenia
6. Rash/Allergic reaction

Front 18

Natalizumab

Back 18

Natalizumab
- Humanized monoclonal antiobody to alpha-4 integrin for Crohn's disease
- Helps to prevent relapse in MS

- Should not use more than one therapy

Front 19

Entaracept
Class?
Mechanism?
Clinical Use?

Back 19

Entaracept
Class: Fusion Protein - Biological Modifier

Mechanism: construct of TNF-alpha receptor binding site

Clinical Uses:
1. RA
2. Crohn's

Front 20

Abatacept
Class?
Mechanism?

Back 20

Abatacept

Class: Fusion Protein - Biological Modifier

Mechanism: costimulation modulator - fusion protein to CTLA-4

Front 21

Biological Modifiers
Side Effects?

Back 21

Side effects of biological modifiers

1. Secondary to Injection site:
- Pain, swelling/itch, Fever/chills/Rash
2. Major Side effect is infection
3. Additional Side Effects: Nausea, vomiting, headache, abdominal pain

- These agents are contraindicated in sepsis
- Potential for malignancy

- Infliximab reported to cause anaphylaxis or Lupus-like syndrome on rare occasions

Front 22

Colchicine
Mechanism?
Clinical Use?

Back 22

Colchicine

Mechanism:
1. Recommended use in patients when NSAIDs are not effective or are contraindicated
2. Not Uricosuric
3. Inhibits cell migration and thus decreases inflammatory response

Clinical Uses: GOUT - only use on an as needed basis

Side Effects - tend to limit therapy
1. GI distress with abdominal pain
2. Myopathy and Neuropathy associated with weakness in patients
3. Blood dyscrasias

Front 23

Probenecid, Sulfinpyrazone
Mechanism?
Use?
Toxicity?

Back 23

Probenecid, Sulfipyrazone

Mechanism: Increase renal clearance of Uric acid

Clinical: GOUT

Toxicity:
1. Can percipitate uric acid crystals in renal tubules
2. Drugs can produce rash and hypersensitivity reactions
3. GI irritation can occur so caution should be taken with patients with peptic ulcers

Front 24

Allopurinol, Febuxostat
Mechanism?
Use?
Toxicity?

Back 24

Allopurinol, Febuxostat

Mechanism:
1. Decreases Uric Acid production by inhibiting Xanthine Oxidase

Use: GOUT

Toxicity:
1. Rash, hypersensitivity reactions
2. Fever, Malaise, muscle aches
3. Rarely see leukopenia

Front 25

Adalimumab
Class?
Use?

Back 25

Adalimumab

Class: Antidbody to TNF-alpha

Use: Rheumatoid Arthritis, Crohn's Disease, Ankylosing Spondylitis

Front 26

Infliximab
Class?
Use?

Back 26

Infliximab

Class: Antibody to TNF-alpha

Use: Crohn's Disease

Front 27

Golimumab
Class?
Use?

Back 27

Golimumab

Class: Antibody to TNF-alpha

Use: Rheumatoid Arthritis, Psortiatic Arthritis, Ankylosing Spodylitis